The present invention relates to a novel prophylactic and curing composition for arteriosclerosis, a use of an 8-chlorobenzothiazepine compound for preparing said composition and a method of the prophylaxis or treatment of arteriosclerosis. 2-(4-Methoxyphenyl)-3-alkanoyloxy-5-[2-(dialkylamino)ethyl]-8-chloro-2,3-d ihydro-1,5-benzothiazepin-4(5H)-one is a known compound, and it has been known to have excellent hypotensive activity and/or cerebral and coronary vasodilating activity (Japanese Unexamined Patent Publication No. 225174/1984).
However, in the prior art, it has never been known that this compound shows anti-arteriosclerosis activity.
Arteriosclerosis is pathologically classified into the three groups of atherosclerosis, Monkeberg's sclerosis (medial sclerosis) and arteriolosclerosis. Atherosclerosis is characterized by lipid deposition and plaque formation in the intima of e.g., coronary artery, basilar artery, renal artery, thoracic aorta or abdominal aorta. Monkeberg's sclerosis is frequently observed in medium-sized arteries in extremities, such as e.g., femoral artery, and characterized by calcification of arterial media. Arteriolosclerosis is a sclerotic change which is observed in arterioles in e.g. the kidney, adrenal gland, spleen, ovary or pancreas.
In recent years, advanced studies have been made about these arteriosclerosis, and it has been considered that non-limited growth of medial smooth muscle cells in the intima of blood vessels and abnormal accumulation of cholesterol within cells can be the causes for such arteriosclerosis, and the relationship between such causes and prostacyclin (PGI.sub.2) is now of interest. For example, when a rabbit is fed with a cholesterol-rich diet, it has been known that prostacyclin producing ability of artery is lowered together with the progress of arteriosclerosis of said rabbit.
It is also known that prostacyclin producing ability is lowered at the arteriosclerotic lesion site to a level half or lower of that at normal site [Gendai Iryo (Modern Medical Treatment), 12, 909(1980)].
On the other hand, Hajjar et al report that addition of prostacyclin to a culture system of medial smooth muscle cells from rabbit aorta increases ACEH (Acid cholesteryl ester hydrolase) activity of the cells, whereby deposition of cholesterol within the cells is inhibited [Journal of Clinical Investigation, 70, 479 (1982)]. Further, it is also reported for medial smooth muscle cells from arteriosclerotic lesions that addition of prostacyclin in a culture system lowers the cholesterol content in said cells [Lancet, 2, 521 (1983)].